1. Field of the Invention
The invention relates generally to bioavailability and delivery of therapeutic molecules and, more specifically, to guandinylated cyclic acetals and conjugation of such modified acetals to therapeutic compounds to increase the cellular uptake of the therapeutic compounds.
2. Background Information
Charged molecules over 500 attomicron typically exhibit poor bioavailability. This limits the delivery of many therapeutically active molecules to their intended targets. Polycationic molecules provide important exceptions to this generalization. Modification of Bovine Serum Albumin (BSA) with ethylene diamine produces “cationionized BSA”, a highly effective antigen carrier. Despite its size (over 66,000 attomicron), cationized BSA efficiently enters cells via an unknown path involving adsorptive uptake. More recently, a number of poly-arginine peptides, peptoids, and peptidomimetics, have been found to exhibit highly efficient uptake into a wide range of mammalian cell types. The conjugation of such poly-Arg peptides to large molecules can facilitate the transduction of peptide, protein, and nucleic acid, conjugates into cells. The mechanism responsible for poly-Arg mediated transport is still unclear, but may involve a receptor mediated, non-endocytotic route.
Thus, an opportunity exists for exploiting such a poly-arginine peptide-like transduction mechanism for efficient uptake of therapeutically active molecules by eukaryotic cells.